The Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh.

BACKGROUND: Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity. OBJECTIVES: The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy. POPULATION: The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018-2019. DESIGN: Prospective, longitudinal pregnancy and birth cohort. METHODS: We conducted home visits to enrol pregnant women in the late first or early second trimester (11-17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants. PRELIMINARY RESULTS: We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 µg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1) µg/L and 33.1 (19.6, 56.5) µg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴ = 0.72) among women with water arsenic ≥ median but weakly correlated (⍴ = 0.17) among women with water arsenic < median. CONCLUSIONS: The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. REGISTRATION: NCT03930017.

Seasonal influenza vaccine uptake among healthcare workers in tertiary care hospitals, Bangladesh: Study protocol for influenza vaccine supply and awareness intervention.

BACKGROUND: Healthcare workers (HCWs), such as doctors, nurses, and support staffs involved in direct or indirect patient care, are at increased risk of influenza virus infections due to occupational exposures. Vaccination is the most effective way to prevent influenza. Despite the World Health Organization (WHO) recommendations, Bangladesh lacks a seasonal influenza vaccination policy for HCWs, and thus vaccination rates remain low. The current project aims to investigate the effect of interventions on influenza vaccine awareness and availability of vaccine supply, explore HCWs' knowledge and perceptions about influenza vaccination, understand the barriers and motivators for influenza vaccine uptake, and understand policymakers' views on the practicality of influenza vaccination among HCWs. METHOD: We will conduct the study at four tertiary care teaching hospitals in Bangladesh, using a cluster randomized controlled trial approach, with the hospital as the unit of randomization and intervention. The study population will include all types of HCWs.The four different types of intervention will be randomly allocated and implemented in four study hospitals separately. The four interventions will be: i) ensuring the availability of influenza vaccine supply; ii) developing influenza vaccine awareness; iii) both ensuring influenza vaccine supply and developing influenza vaccine awareness and iv) control arm with no intervention. Both quantitative and qualitative approaches will be applied to assess the intervention effect. We will estimate the Difference in Differences (DID) with 95% CI of the proportion of vaccine uptake between each intervention and control (non-intervention) arm, adjusting for the clustering effect. The qualitative data will be summarised using a framework matrix method. DISCUSSION: The results of this study will inform the development and implementation of a context-specific strategy to enhance influenza vaccination rates among Bangladeshi HCWs. TRIAL REGISTRATION: Clinicaltrials.gov NCT05521763. Version 2.0 was registered in September 2022, and the first participant enrolled in March 2022. Retrospectively registered.

Assessment of immunity to polio among Rohingya children in Cox's Bazar, Bangladesh, 2018: A cross-sectional survey.

BACKGROUND: We performed a cross-sectional survey in April-May 2018 among Rohingya in Cox's Bazar, Bangladesh, to assess polio immunity and inform vaccination strategies. METHODS AND FINDINGS: Rohingya children aged 1-6 years (younger group) and 7-14 years (older group) were selected using multi-stage cluster sampling in makeshift settlements and simple random sampling in Nayapara registered camp. Surveyors asked parents/caregivers if the child received any oral poliovirus vaccine (OPV) in Myanmar and, for younger children, if the child received vaccine in any of the 5 campaigns delivering bivalent OPV (serotypes 1 and 3) conducted during September 2017-April 2018 in Cox's Bazar. Dried blood spot (DBS) specimens were tested for neutralizing antibodies to poliovirus types 1, 2, and 3 in 580 younger and 297 older children. Titers ≥ 1:8 were considered protective. Among 632 children (335 aged 1-6 years, 297 aged 7-14 years) enrolled in the study in makeshift settlements, 51% were male and 89% had arrived after August 9, 2017. Among 245 children (all aged 1-6 years) enrolled in the study in Nayapara, 54% were male and 10% had arrived after August 9, 2017. Among younger children, 74% in makeshift settlements and 92% in Nayapara received >3 bivalent OPV doses in campaigns. Type 1 seroprevalence was 85% (95% CI 80%-89%) among younger children and 91% (95% CI 86%-95%) among older children in makeshift settlements, and 92% (88%-95%) among younger children in Nayapara. Type 2 seroprevalence was lower among younger children than older children in makeshift settlements (74% [95% CI 68%-79%] versus 97% [95% CI 94%-99%], p < 0.001), and was 69% (95% CI 63%-74%) among younger children in Nayapara. Type 3 seroprevalence was below 75% for both age groups and areas. The limitations of this study are unknown routine immunization history and poor retention of vaccination cards. CONCLUSIONS: Younger Rohingya children had immunity gaps to all 3 polio serotypes and should be targeted by future campaigns and catch-up routine immunization. DBS collection can enhance the reliability of assessments of outbreak risk and vaccination strategy impact in emergency settings.

Development of an RNA Strand-Specific Hybridization Assay To Differentiate Replicating versus Nonreplicating Influenza A Viruses.

Replication of influenza A virus (IAV) from negative-sense viral RNA (vRNA) requires the generation of positive-sense RNA (+RNA). Most molecular assays, such as conventional real-time reverse transcriptase PCR (rRT-PCR), detect total RNA in a sample without differentiating vRNA from +RNA. These assays are not designed to distinguish IAV infection versus exposure of an individual to an environment enriched with IAVs but wherein no viral replication occurs. We therefore developed a strand-specific hybridization (SSH) assay that differentiates between vRNA and +RNA and quantifies relative levels of each RNA species. The SSH assay exhibited a linearity of 7 logs with a lower limit of detection of 6.0 × 102 copies of molecules per reaction. No signal was detected in samples with a high load of nontarget template or influenza B virus, demonstrating assay specificity. IAV +RNA was detected 2 to 4 h postinoculation of MDCK cells, whereas synthesis of cold-adapted IAV +RNA was significantly impaired at 37°C. The SSH assay was then used to test IAV rRT-PCR positive nasopharyngeal specimens collected from individuals exposed to IAV at swine exhibitions (n = 7) or while working at live bird markets (n = 2). The SSH assay was able to differentiate vRNA and +RNA in samples collected from infected, symptomatic individuals versus individuals who were exposed to IAV in the environment but had no active viral replication. Data generated with this technique, especially when coupled with clinical data and assessment of seroconversion, will facilitate differentiation of actual IAV infection with replicating virus versus individuals exposed to high levels of environmental contamination but without virus infection.

Mild Respiratory Illness Among Young Children Caused by Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in Dhaka, Bangladesh, 2011.

Background: In March 2011, a multidisciplinary team investigated 2 human cases of highly pathogenic avian influenza A(H5N1) virus infection, detected through population-based active surveillance for influenza in Bangladesh, to assess transmission and contain further spread. Methods: We collected clinical and exposure history of the case patients and monitored persons coming within 1 m of a case patient during their infectious period. Nasopharyngeal wash specimens from case patients and contacts were tested with real-time reverse-transcription polymerase chain reaction, and virus culture and isolates were characterized. Serum samples were tested with microneutralization and hemagglutination inhibition assays. We tested poultry, wild bird, and environmental samples from case patient households and surrounding areas for influenza viruses. Results: Two previously healthy case patients, aged 13 and 31 months, had influenzalike illness and fully recovered. They had contact with poultry 7 and 10 days before illness onset, respectively. None of their 57 contacts were subsequently ill. Clade 2.2.2.1 highly pathogenic avian influenza H5N1 viruses were isolated from the case patients and from chicken fecal samples collected at the live bird markets near the patients' dwellings. Conclusion: Identification of H5N1 cases through population-based surveillance suggests possible additional undetected cases throughout Bangladesh and highlights the importance of surveillance for mild respiratory illness among populations frequently exposed to infected poultry.

Prevalence and clinical presentation of Rickettsia, Coxiella, Leptospira, Bartonella and chikungunya virus infections among hospital-based febrile patients from December 2008 to November 2009 in Bangladesh.

BACKGROUND: We conducted a study to identify Rickettsia, Coxiella, Leptospira, Bartonella, and Chikungunya virus infections among febrile patients presenting at hospitals in Bangladesh. METHODS: We collected blood samples from patients at six tertiary hospitals from December 2008 to November 2009 and performed laboratory tests at the United States Centers for Disease Control and Prevention (CDC). RESULTS: Out of 720 enrolled patients, 263 (37%) were infected with Rickettsia; 132 patients had immunofluorescence antibody titer >64 against spotted fever, 63 patients against scrub typhus fever and 10 patients against typhus fever. Ten patients were identified with Coxiella. We isolated Leptospira from two patients and Bartonella from one patient. Ten patients had antibodies against Chikungunya virus. The proportion of patients who died was higher with rickettsial fever (5%) compared to those without a diagnosis of rickettsial infection (2%). None of the patients were initially diagnosed with rickettsial fever. CONCLUSIONS: Rickettsial infections are frequent yet under-recognized cause of febrile illness in Bangladesh. Clinical guidelines should be revised so that local clinicians can diagnose rickettsial infections and provide appropriate drug treatment.

Low-Cost National Media-Based Surveillance System for Public Health Events, Bangladesh.

We assessed a media-based public health surveillance system in Bangladesh during 2010-2011. The system is a highly effective, low-cost, locally appropriate, and sustainable outbreak detection tool that could be used in other low-income, resource-poor settings to meet the capacity for surveillance outlined in the International Health Regulations 2005.

Oral cholera vaccine coverage evaluation survey: Forcibly Displaced Myanmar Nationals and host community in Cox's Bazar, Bangladesh.

Introduction: Cholera remains a significant public health concern in many parts of the world, particularly in areas with poor sanitation and hygiene. Bangladesh and other impoverished nations have been severely affected by cholera outbreaks, especially in areas with a high population density. In order to mitigate the spread of cholera, oral cholera vaccines (OCVs) are recommended as a prophylactic measure. In May 2018, 775,666 of the Forcibly Displaced Myanmar Nationals (FDMN) in the registered and makeshift camps and 103,605 of the residents in the host community received two doses of OCV ShancholTM in Cox's Bazar, Bangladesh, because the conditions in the area favored the transmission of cholera and other waterborne diseases. This study aimed to assess the coverage of OCV among the FDMN and the host community in Cox's Bazar. Methods: In August 2018, we enrolled 4,240 respondents for this study following the "World Health Organization (WHO) Vaccination Coverage Cluster Surveys: Reference Manual (2018)." The coverage survey was conducted with three strata of the population: the host community from the Teknaf Upazila, the registered camp, and the makeshift camp from the Ukhia Upazila. We collected information regarding OCV coverage, demographic characteristics, and knowledge and behaviors of people toward the vaccine. The data were analyzed using descriptive statistics. Results: According to our study, the overall OCV coverage was 85%, with 68% in the host community, 91% in the registered camp, and 98% in the makeshift camp. The lower coverage in the host community was due to residents unaware of the vaccination campaign, the unavailability of vaccines, and unaware where to go for vaccination. Discussion: Our findings demonstrate that the OCV campaign in the FDMN camps was successful, reaching over 90% coverage, while coverage in the host community was much lower. In order to make sure that OCV vaccination efforts are reaching the target population and having the desired impact, our study emphasizes the need to inform the target population of when and where to get vaccinated.

Lessons learned from identifying clusters of severe acute respiratory infections with influenza sentinel surveillance, Bangladesh, 2009-2020.

Background: We explored whether hospital-based surveillance is useful in detecting severe acute respiratory infection (SARI) clusters and how often these events result in outbreak investigation and community mitigation. Methods: During May 2009-December 2020, physicians at 14 sentinel hospitals prospectively identified SARI clusters (i.e., ≥2 SARI cases who developed symptoms ≤10 days of each other and lived <30 min walk or <3 km from each other). Oropharyngeal and nasopharyngeal swabs were tested for influenza and other respiratory viruses by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We describe the demographic of persons within clusters, laboratory results, and outbreak investigations. Results: Field staff identified 464 clusters comprising 1427 SARI cases (range 0-13 clusters per month). Sixty percent of clusters had three, 23% had two, and 17% had ≥4 cases. Their median age was 2 years (inter-quartile range [IQR] 0.4-25) and 63% were male. Laboratory results were available for the 464 clusters with a median of 9 days (IQR = 6-13 days) after cluster identification. Less than one in five clusters had cases that tested positive for the same virus: respiratory syncytial virus (RSV) in 58 (13%), influenza viruses in 24 (5%), human metapneumovirus (HMPV) in five (1%), human parainfluenza virus (HPIV) in three (0.6%), adenovirus in two (0.4%). While 102/464 (22%) had poultry exposure, none tested positive for influenza A (H5N1) or A (H7N9). None of the 464 clusters led to field deployments for outbreak response. Conclusions: For 11 years, none of the hundreds of identified clusters led to an emergency response. The value of this event-based surveillance might be improved by seeking larger clusters, with stronger epidemiologic ties or decedents.

Appearance of tolerance-induction and non-inflammatory SARS-CoV-2 spike-specific IgG4 antibodies after COVID-19 booster vaccinations.

Background: Understanding the characteristics of the humoral immune responses following COVID-19 vaccinations is crucial for refining vaccination strategies and predicting immune responses to emerging SARS-CoV-2 variants. Methods: A longitudinal analysis of SARS-CoV-2 spike receptor binding domain (RBD) specific IgG antibody responses, encompassing IgG subclasses IgG1, IgG2, IgG3, and IgG4 was performed. Participants received four mRNA vaccine doses (group 1; n=10) or two ChAdOx1 nCoV-19 and two mRNA booster doses (group 2; n=19) in Bangladesh over two years. Results: Findings demonstrate robust IgG responses after primary Covishield or mRNA doses; declining to baseline within six months. First mRNA booster restored and surpassed primary IgG responses but waned after six months. Surprisingly, a second mRNA booster did not increase IgG levels further. Comprehensive IgG subclass analysis showed primary Covishield/mRNA vaccination generated predominantly IgG1 responses with limited IgG2/IgG3, Remarkably, IgG4 responses exhibited a distinct pattern. IgG4 remained undetectable initially but increased extensively six months after the second mRNA dose, eventually replacing IgG1 after the 3rd/4th mRNA doses. Conversely, initial Covishield recipients lack IgG4, surged post-second mRNA booster. Notably, mRNA-vaccinated individuals displayed earlier, robust IgG4 levels post first mRNA booster versus Covishield counterparts. IgG1 to IgG4 ratios decreased with increasing doses, most pronounced with four mRNA doses. This study highlights IgG response kinetics, influenced by vaccine type and doses, impacting immunological tolerance and IgG4 induction, shaping future vaccination strategies. Conclusions: This study highlights the dynamics of IgG responses dependent on vaccine type and number of doses, leading to immunological tolerance and IgG4 induction, and shaping future vaccination strategies.

Early detection of pandemic (H1N1) 2009, Bangladesh.

To explore Bangladesh's ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June-July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.

Influenza-associated mortality in 2009 in four sentinel sites in Bangladesh.

OBJECTIVE: To estimate influenza-associated mortality in Bangladesh in 2009. METHODS: In four hospitals in Bangladesh, respiratory samples were collected twice a month throughout 2009 from inpatients aged < 5 years with severe pneumonia and from older inpatients with severe acute respiratory infection. The samples were tested for influenza virus ribonucleic acid (RNA) using polymerase chain reaction. The deaths in 2009 in five randomly selected unions (the smallest administrative units in Bangladesh) in each hospital's catchment area were then investigated using formal records and informal group discussions. The deaths of those who had reportedly died within 14 days of suddenly developing fever with cough and/or a sore throat were assumed to be influenza-associated. The rate of such deaths in 2009 in each of the catchment areas was then estimated from the number of apparently influenza-associated deaths in the sampled unions, the proportion of the sampled inpatients in the local hospital who tested positive for influenza virus RNA, and the estimated number of residents of the sampled unions. FINDINGS: Of the 2500 people known to have died in 2009 in all 20 study unions, 346 (14%) reportedly had fever with cough and/or sore throat within 14 days of their deaths. The estimated mean annual influenza-associated mortality in these unions was 11 per 100,000 population: 1.5, 4.0 and 125 deaths per 100,000 among those aged < 5, 5-59 and > 59 years, respectively. CONCLUSION: The highest burden of influenza-associated mortality in Bangladesh in 2009 was among the elderly.

Incidence of influenza-like illness and severe acute respiratory infection during three influenza seasons in Bangladesh, 2008-2010.

OBJECTIVE: To determine how much influenza contributes to severe acute respiratory illness (SARI), a leading cause of death in children, among people of all ages in Bangladesh. METHODS: Physicians obtained nasal and throat swabs to test for influenza virus from patients who were hospitalized within 7 days of the onset of severe acute respiratory infection (SARI) or who consulted as outpatients for influenza-like illness (ILI). A community health care utilization survey was conducted to determine the proportion of hospital catchment area residents who sought care at study hospitals and calculate the incidence of influenza using this denominator. FINDINGS: The estimated incidence of SARI associated with influenza in children < 5 years old was 6.7 (95% confidence interval, CI: 0-18.3); 4.4 (95% CI: 0-13.4) and 6.5 per 1000 person-years (95% CI: 0-8.3/1000) during the 2008, 2009 and 2010 influenza seasons, respectively. The incidence of SARI in people aged ≥ 5 years was 1.1 (95% CI: 0.4-2.0) and 1.3 (95% CI: 0.5-2.2) per 10,000 person-years during 2009 and 2010, respectively. The incidence of medically attended, laboratory-confirmed seasonal influenza in outpatients with ILI was 10 (95% CI: 8-14), 6.6 (95% CI: 5-9) and 17 per 100 person-years (95% CI: 13-22) during the 2008, 2009 and 2010 influenza seasons, respectively. CONCLUSION: Influenza-like illness is a frequent cause of consultation in the outpatient setting in Bangladesh. Children aged less than 5 years are hospitalized for influenza in greater proportions than children in other age groups.

Resumen OBJETIVO: Determinar en qué medida contribuye la gripe a la enfermedad respiratoria aguda grave (ERAG), una de las principales causas de muerte infantil, en personas de todas las edades en Bangladesh. MÉTODOS: Los médicos tomaron muestras de exudado nasal y faríngeo para realizar la prueba del virus de la gripe en pacientes que estuvieron hospitalizados en los 7 días posteriores al inicio de la infección respiratoria agua grave (IRAG) o que acudieron a consulta como pacientes ambulatorios por síndrome gripal (SG). Se llevó a cabo un estudio sobre el uso de la asistencia sanitaria comunitaria para determinar la proporción de residentes del área de cobertura del hospital que solicitaron asistencia médica en hospitales pertenecientes al estudio y se calculó la incidencia de la gripe con este denominador. RESULTADOS: La incidencia estimada de la IRAG asociada con la gripe en niños menores de 5 años fue del 6,7 (95% de intervalo de confianza, IC: 0-18,3); 4,4 (95% IC: 0-13,4) y 6,5 por 1000 años-persona (95% IC: 0-8,3/1000) durante las temporadas de gripe de 2008, 2009 y 2010, respectivamente. La incidencia de la IRAG en las personas con una edad igual o superior a 5 años fue del 1,1 (95% IC: 0,4- 2,0) y 1,3 (95% IC: 0,5-2,2) por 10 000 años-persona durante 2009 y 2010, respectivamente. La incidencia de la gripe de temporada tratada médicamente y confirmada en laboratorio en pacientes ambulatorios con SG fue de 10 (95% IC: 8-14); 6,6 (95% IC: 5-9) y 17 por 100 años-persona (95% IC: 13-22/1000) durante las temporadas de gripe de 2008, 2009 y 2010, respectivamente. CONCLUSIÓN: El síndrome gripal es una causa frecuente de consulta en los centros ambulatorios en Bangladesh. La proporción de niños menores de 5 años hospitalizados por gripe es mayor que la de niños en otros grupos de edad.

Résumé OBJECTIF: Déterminer l'impact de la grippe sur le syndrome respiratoire aigu sévère (SRAS), une cause majeure de la mortalité chez les enfants, chez les personnes de tous les âges au Bangladesh. MÉTHODES: Les médecins ont obtenu des écouvillons de prélèvement de nez et de gorge afin de tester le virus de la grippe chez des patients qui avaient été hospitalisés dans les 7 jours suivants l'apparition de l'infection respiratoire aiguë sévère (SRAS) ou qui avaient eu une consultation déambulatoire pour un syndrome de type grippal (STG). Une enquête sur l'utilisation des soins de santé communautaires a été effectuée afin de définir la proportion des riverains de la circonscription hospitalière, qui avaient reçu des soins dans les hôpitaux universitaires, et afin de calculer l'incidence de la grippe à l'aide de ce dénominateur. RÉSULTATS: L'estimation de l'incidence du SRAS associé à la grippe chez les enfants de moins de 5 ans était de 6,7 (intervalle de confiance de 95%, IC: 0-18.3); de 4,4 (IC de 95%: 0-13.4) et de 6,5 pour 1 000 personnes-années (IC de 95%: 0-8.3/1000) lors des saisons de la grippe de 2008, 2009 et 2010, respectivement. L'incidence du SRAS chez les personnes âgées de plus de 5 ans était de 1,1 (IC de 95%: 0.4-2.0) et 1,3 (IC de 95%: 0.5-2.2) pour 10 000 personnes-années en 2009 et 2010, respectivement. L'incidence de la grippe saisonnière traitée médicalement et confirmée en laboratoire chez les patients en consultation ambulatoire souffrant du STG était de 10 (IC de 95%: 8-14), 6,6 (IC de 95%: 5-9) et de 17 pour 100 personnes-années (IC de 95%: 13-22) lors des saisons de la grippe de 2008, 2009 et 2010, respectivement. CONCLUSION: Le syndrome de type grippal est une cause fréquente de consultation dans la configuration de la consultation ambulatoire au Bangladesh. Les enfants de moins de 5 ans sont hospitalisés pour la grippe dans des proportions supérieures aux enfants des autres groupes d'âge.

Rapid antigen testing by community health workers for detection of SARS-CoV-2 in Dhaka, Bangladesh: a cross-sectional study.

OBJECTIVE: To evaluate the diagnostic performance and feasibility of rapid antigen testing for SARS-CoV-2 detection in low-income communities. DESIGN: We conducted a cross-sectional community-based diagnostic accuracy study. Community health workers, who were trained and supervised by medical technicians, performed rapid antigen tests on symptomatic individuals, and up to two additional household members in their households and diagnostic results were calibrated against the gold standard RT-PCR. SETTING: Low-income communities in Dhaka, Bangladesh. PARTICIPANTS: Between 19 May 2021 and 11 July 2021, 1240 nasal and saliva samples were collected from symptomatic individuals and 993 samples from additional household members (up to two from one household). RESULTS: The sensitivity of rapid antigen tests was 0.68 on nasal samples (95% CI 0.62 to 0.73) and 0.41 on saliva (95% CI 0.35 to 0.46), with specificity also higher on nasal samples (0.98, 95% CI 0.97 to 0.99) than saliva (0.87, 95% CI 0.85 to 0.90). Testing up to two additional household members increased sensitivity to 0.71 on nasal samples (95% CI 0.65 to 0.76), but reduced specificity (0.96, 95% CI 0.94 to 0.97). Sensitivity on saliva rose to 0.48 (95% CI 0.42 to 0.54) with two additional household members tested but remained lower than sensitivity on nasal samples. During the study period, testing in these low-income communities increased fourfold through the mobilisation of community health workers for sample collection. CONCLUSIONS: Rapid antigen testing on nasal swabs can be effectively performed by community health workers yielding equivalent sensitivity and specificity to the literature. Household testing by community health workers in low-resource settings is an inexpensive approach that can increase testing capacity, accessibility and the effectiveness of control measures through immediately actionable results.

Covishield vaccine induces robust immune responses in Bangladeshi adults.

Objective: To evaluate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibody responses after Covishield vaccination for 6 months after vaccination. Design: SARS-CoV-2-specific antibody responses were assessed by enzyme-linked immunosorbent assay of the recombinant receptor-binding domain of SARS-CoV-2 in 381 adults given the Covishield vaccine at baseline (n=119), 1 month (n=126) and 2 months (n=75) after the first dose, 1 month after the second dose (n=161), and monthly for 3 additional months. Results: Over 51% of participants were seropositive at baseline (before vaccination with Covishield), and almost all participants (159/161) became seropositive 1 month after the second dose. Antibody levels peaked 1 month after receipt of the second dose of vaccine, and decreased by 4 months after the first dose; the lowest responses were found 6 months after the first dose, although antibody responses and responder frequencies remained significantly higher compared with baseline (P<0.0001). Compared with younger participants, older participants had lower antibody responses 6 months after the first dose of vaccine (P<0.05). Participants who had previous SARS-CoV-2 infection showed robust higher antibody responses after vaccination. Conclusions: These findings help to elucidate the longevity of vaccine-specific antibody responses following vaccination with Covishield, and provide information relevant to the planning of booster doses after the initial two doses of vaccine.

Seasonality of influenza and coseasonality with avian influenza in Bangladesh, 2010-19: a retrospective, time-series analysis.

BACKGROUND: Seasonal and avian influenza viruses circulate among human and poultry populations in Bangladesh. However, the epidemiology of influenza is not well defined in this setting. We aimed to characterise influenza seasonality, examine regional heterogeneity in transmission, and evaluate coseasonality between circulating influenza viruses in Bangladesh. METHODS: In this retrospective, time-series study, we used data collected between January, 2010, and December, 2019, from 32 hospital-based influenza surveillance sites across Bangladesh. We estimated influenza peak timing and intensity in ten regions using negative binomial harmonic regression models, and applied meta-analytic methods to determine whether seasonality differed across regions. Using live bird market surveillance data in Dhaka, Bangladesh, we estimated avian influenza seasonality and examined coseasonality between human and avian influenza viruses. FINDINGS: Over the 10-year study period, we included 8790 human influenza cases and identified a distinct influenza season, with an annual peak in June to July each year (peak calendar week 27·6, 95% CI 26·7-28·6). Epidemic timing varied by region (I2=93·9%; p<0·0001), with metropolitan regions peaking earlier and epidemic spread following a spatial diffusion pattern based on geographical proximity. Comparatively, avian influenza displayed weak seasonality, with moderate year-round transmission and a small peak in April (peak calendar week 14·9, 95% CI 13·2-17·0), which was out of phase with influenza peaks in humans. INTERPRETATION: In Bangladesh, influenza prevention and control activities could be timed with annual seasonality, and regional heterogeneity should be considered in health resource planning. Year-round avian influenza transmission poses a risk for viral spillover, and targeted efforts will be crucial for mitigating potential reassortment and future pandemic threats. FUNDING: Canadian Institute of Health Research Vanier Canada Graduate Scholarship.

Combining rapid antigen testing and syndromic surveillance improves community-based COVID-19 detection in a low-income country.

Diagnostics for COVID-19 detection are limited in many settings. Syndromic surveillance is often the only means to identify cases but lacks specificity. Rapid antigen testing is inexpensive and easy-to-deploy but can lack sensitivity. We examine how combining these approaches can improve surveillance for guiding interventions in low-income communities in Dhaka, Bangladesh. Rapid-antigen-testing with PCR validation was performed on 1172 symptomatically-identified individuals in their homes. Statistical models were fitted to predict PCR-status using rapid-antigen-test results, syndromic data, and their combination. Under contrasting epidemiological scenarios, the models' predictive and classification performance was evaluated. Models combining rapid-antigen-testing and syndromic data yielded equal-to-better performance to rapid-antigen-test-only models across all scenarios with their best performance in the epidemic growth scenario. These results show that drawing on complementary strengths across rapid diagnostics, improves COVID-19 detection, and reduces false-positive and -negative diagnoses to match local requirements; improvements achievable without additional expense, or changes for patients or practitioners.

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh.

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June−September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 (p = 0.01) and 28 (p = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable (p > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.

Seroprevalence of SARS-CoV-2 antibodies among Forcibly Displaced Myanmar Nationals in Cox's Bazar, Bangladesh 2020: a population-based cross-sectional study.

OBJECTIVES: The study aimed to determine the seroprevalence, the fraction of asymptomatic infections, and risk factors of SARS-CoV-2 infections among the Forcibly Displaced Myanmar Nationals (FDMNs). DESIGN: It was a population-based two-stage cross-sectional study at the level of households. SETTING: The study was conducted in December 2020 among household members of the FDMN population living in the 34 camps of Ukhia and Teknaf Upazila of Cox's Bazar district in Bangladesh. PARTICIPANTS: Among 860 697 FDMNs residing in 187 517 households, 3446 were recruited for the study. One individual aged 1 year or older was randomly selected from each targeted household. PRIMARY AND SECONDARY OUTCOME MEASURES: Blood samples from respondents were tested for total antibodies for SARS-CoV-2 using Wantai ELISA kits, and later positive samples were validated by Kantaro kits. RESULTS: More than half (55.3%) of the respondents were females, aged 23 median (IQR 14-35) years and more than half (58.4%) had no formal education. Overall, 2090 of 3446 study participants tested positive for SARS-CoV-2 antibody. The weighted and test adjusted seroprevalence (95% CI) was 48.3% (45.3% to 51.4%), which did not differ by the sexes. Children (aged 1-17 years) had a significantly lower seroprevalence 38.6% (95% CI 33.8% to 43.4%) compared with adults (58.1%, 95% CI 55.2% to 61.1%). Almost half (45.7%, 95% CI 41.9% to 49.5%) of seropositive individuals reported no relevant symptoms since March 2020. Antibody seroprevalence was higher in those with any comorbidity (57.8%, 95% CI 50.4% to 64.5%) than those without (47.2%, 95% CI 43.9% to 50.4%). Multivariate logistic regression analysis of all subjects identified increasing age and education as risk factors for seropositivity. In children (≤17 years), only age was significantly associated with the infection. CONCLUSIONS: In December 2020, about half of the FDMNs had antibodies against SARS-CoV-2, including those who reported no history of symptoms. Periodic serosurveys are necessary to recommend appropriate public health measures to limit transmission.

Infrastructure alone cannot ensure resilience to weather events in drinking water supplies.

Climate resilient water supplies are those that provide access to drinking water that is sustained through seasons and through extreme events, and where good water quality is also sustained. While surface and groundwater quality are widely understood to vary with rainfall, there is a gap in the evidence on the impact of weather and extremes in rainfall and temperature on drinking water quality, and the role of changes in water system management. A three-country (Bangladesh, Nepal and Tanzania) observational field study tracked 2353 households clustered around 685 water sources across seven different geographies over 14 months. Water quality (E. coli) data was modelled using GEE to account for clustering effects and repeated measures at households. All types of infrastructure were vulnerable to changes in weather, with differences varying between geographies; protected boreholes provided the greatest protection at the point of collection (PoC). Water quality at the point of use (PoU) was vulnerable to changes in weather, through changes in PoC water quality as well as changes in management behaviours, such as safe storage, treatment and cleaning. This is the first study to demonstrate the impact of rainfall and temperature extremes on water quality at the PoC, and the role that weather has on PoU water quality via management behaviours. Climate resilience for water supplies needs to consider the infrastructure as well as the management decisions that are taking place at a community and household level.